Previous work has demonstrated that the endogenously produced purine nucleoside inosine exerts potentially important effects on the heart. These include a positive inotropic action and a coronary dilatation beyond that required by the increase oxygen demand. The myocardial levels exerting these actions may exist in ischemia. The proposed work will explore the actions of inosine and their potential importance in ischemic myocardial and coronary function. Three projects are proposed in dogs: (1) Exploration of the mechanism of the coronary action. Studies will test the hypothesis that a portion of the vascular action is due to inhibition of uptake of endogenously formed adenosine. Myocardial and pericardial perfusate levels of andenosine will be measured during the coronary response to inosine. Other studies using isolated coronary vessels will examine the direct effect of inosine of vessel relaxation. (2) Exploration of the mechanism of the inotropic action. Studies will be performed to determine if the inotropic action is inhibited by verapamil, indicating a membrane effect on calcium influx. Also, studies will determine if the inotropic action is associated with increased myocardial cyclic AMP. Other studies will determine if the inotropic action is inhibited by indomethacin, indicating mediation by prostaglandins. (3) Inotropic and coronary actions in the conscious dog. The dose-responses to intracoronary inosine infusion in the conscious animal will be quantified.